With improved financial and technical supports, many malaria endemic nations are once again considering malaria elimination as their national goal of malaria control. To achieve this ambitious goal, one of the greatest challenges is interruption of malaria transmission worldwide. Sexual development of malaria parasite is essential for transmission of the parasite through mosquitoes. Despite its central role in the life cycle of malaria parasites, the mechanism of sexual development is still poorly understood, and this knowledge gap severely hinders the development of novel tools to interrupt malaria transmission. This project, built on our recent success in creating Plasmodium falciparum lines with male or female gametocytes tagged with a reporter gene, aims to determine the molecular differences between the two sexes of gametocytes. The comprehensive transcriptomic and proteomic data generated from this study will enable systems biology approaches to address the fundamental biology of sexual differentiation in malaria parasites. This information is also deemed critical for the development of novel drugs and vaccines for the interruption of malaria transmission. PUBLIC HEALTH RELEVANCE: Sexual development is obligatory for the transmission of malaria parasites through mosquito vectors. Interruption of malaria transmission is considered one of the greatest challenges during the malaria elimination phase. However, the mechanism of sexual differentiation in malaria parasites is still poorly understood. This project is built onour recent success to genetically manipulate the sexual stage parasites and to sort out the two sexes of the gametocyte stages, aiming to determine the differences between the male and female parasite using advanced high-throughput gene expression and protein identification approaches.